1. Field of the Invention
The present invention pertains to a method preparing substituted and unsubstituted N-hydroxy-2-aminobutane diacid derivatives which can be dehydrated to 2-aminobut-2-ene dioic acid derivatives, which subsequently can be converted to pyridine and quinoline derivatives. Unsubstituted hydroxylamines are reacted with substituted or unsubstituted unsaturated diacid derivatives to produce N-hydroxyaspartic acid derivatives which can be dehydrated to 2-aminobut-2-ene dioic acid derivatives, which can subsequently be reacted with .alpha.,.beta.-unsaturated carbonyl compounds to produce pyridine derivatives. When the hydroxylamine is substituted, with a phenyl group, for example, so that N-phenyl-N-hydroxy-2-aminobutane dicarboxylic acid derivative is produced, this derivative can be dehydrated to form 2-anilinobut-2-ene dicarboxylic acid derivative which can further reacted with a Vilsmeier reagent such as an immonium salt to produce quinoline derivatives.
2. Background Art
N-hydroxyamino acids are valuable precursors for natural amino acids, peptides, herbicides, antibiotics, growth promoting agents, antitumor agents, antifungal agents, and polymers. It has been known that the addition of hydroxylamine to an unsaturated monocarboxylic acid derivative can be used to obtain N-hydroxyamino mono carboxylic acid derivative. However, addition of hydroxylmine to an unsaturated dicarboxylic acid, such as fumaric acid, in the presence of an enzyme does not successfully result in the isolation of N-hydroxyaspartic acid, as reported in "Progress in the Chemistry of Organic Natural Products", L. F. Alves et al., Springer-Verlag (1988), page 230. Indeed, the utilization of enzyme extracts, such as Bacillus caderas or Proteus vulgaris also does not yield success in isolating this desired product, but resort must be made, through utilization of a benzyl group, to protect the hydroxylamine moiety as reported by Kolasa, Can. J. Chem., Vol. 63, 2139 (1985). Such methods are cumbersome and involve the removal of protecting groups rather than employing hydroxylamine or a salt thereof directly.
K. Bashceruddin et al., Synthetic Communications, 9, 705-712 (1979) reports the questionable result of obtaining of N-hydroxyaspartic acids of greatly different melting points from maleic acid and fumaric acid, utilizing hydroxylamine. The reaction conditions for such conversion(s) are not disclosed, nor is revealed the criticality involved for obtaining N-hydroxyaspartic acid or its derivatives, namely a critical pH. Furthermore, the only relevant reaction conditions revealed in this publication, those for preparation of N-hydroxy-3-amino-3-(p-nitrophenyl)propionic acid from p-nitrocinnamic acid, do not yield N-hydroxyaspartic acid.
Literature methods for preparing 5,6-dialkyl and 5-alkyl-6-arylpyfidine-2,-3-dicarboxylic acids and esters are limited and often require oxidation of alkyl or aryl substituents at positions 2 and 3 in order to obtain diacids. Recently there has been disclosed a method for the preparation of substituted and disubstituted pyridine-2,3-dicarboxylic acid esters and 2-alkylnicotinates utilizing .alpha.-halo-.beta.-ketoesters and .alpha.,.beta.-unsaturated aldehydes or ketones in the presence of an ammonium salt. The use of .alpha.-halo-.beta.-ketoesters is not desired due to the fact that such materials are usually costly and unstable.
U.S. Pat. No. 4,723,011 discloses preparation of substituted and disubstituted pyridine-2,3-dicarboxylates by the reaction of an .alpha.-halo-.beta.-ketoester such as chloro-diethyloxaloacetate (chloro-DOX) and an .alpha., .beta.-unsaturated aldehyde or ketone such as 2-ethylacrolein in the presence of at least 2 molar equivalents of an ammonium salt in order to produce the desired compounds.
U.S. Pat. No. 4,816,588 discloses and claims a process for preparing pyridine-2,3-dicarboxylic acids by the oxidation of 8-substituted quinolines.
European Patent Application No. 274,379 published Jul. 13, 1988 discloses two processes for producing pyridine-2,3-dicarboxylic acid compounds. One process seems similar to that previously described in U.S. Pat. No. 4,723,011 and the other process involves reacting an .alpha.,.beta.-unsaturated aldehyde or ketone with various aminomaleates or aminofumarates such as diethyl aminomaleate.
European Patent Application No. 299,362 published Jan. 18, 1989 also discloses the same reaction.
U.S. Pat. No. 4,675,432 to Donald R. Maulding, issued Jun. 23, 1987 describes a method for the preparation of anilinofumarate. A dichlorosuccinate is reacted with a molar equivalent of aniline in an inert organic solvent and with two or more molar equivalents of an aqueous base in the presence of a phase transfer catalyst to produce the anilinofumerate.
U.S. Pat. No. 4,656,283 to Robert F. Doehner, Jr., issued Apr. 7, 1987 describes a method for the preparation of alkyl esters of substituted 2-methyl-quinoline-3-carboxylic acid and quinoline-2,3-dicarboxylic acid as well as dialkyl 3-(substituted)-phenylaminobut-2-ene-dioates. An appropriately substituted aniline is reacted with approximately an equimolar amount of a keto-ester to produce the products above-described.
Although the methods described above are useful for producing some of the reaction products produced by the method of the present invention; due to the broad utility of the reaction products of the present invention, as nutrient supplements, and as intermediaries in the production of pharmaceuticals, dyes and pigments and herbicides, any improvement in the method of production is of tremendous potential economic significance.